Diketene → (S)-5-[(3,5-bis-trifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-5-(3,5-bis-trifluoromethyl-benzylamino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (Example 3, Step 14) (1.0 g, 1.75 mmol) and 4-dimethylaminopyridine (25 mg, 0.21 mmol) in dry tetrahydrofuran (10 mL) at 0° C. under a nitrogen atmosphere, add diketene (0.147 mL, 1.93 mmol). After stirring 1.5 h at 0° C., remove the solvent under reduced pressure. Purify the by flash chromatography, eluting with hexanes/ethyl acetate (20:1 to 1:2), to provide the title compound as an off-white solid (1.12 g, 97%). TLC Rf 0.40 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.10-2.10 (m, 13H), 2.29 (s, 3H), 2.52 (s, 3H), 3.41-3.53 (m, 1H), 4.14-4.54 (m, 4H), 4.89-5.12 (m, 1H), 5.57-5.69 (m, 1H), 6.89 (s, 1H), 7.24-7.92 (m, 4H).

Provenance & Evidence